Orthopedics and Muscular
system: Current Research
Robinson et al., Orthop Muscul Syst 2014, 3:4
http://dx.doi.org/10.4172/2161-0533.1000e113
Editorial
Open Access
Platelet-Rich Plasma Therapies in Lateral Epicondylitis: Are we Asking the
Right Questions?
Cal Robinson1,2*, Gopinath Mathavan3 and Anand Pillai2
1University
of Manchester, Manchester, UK
2University
Hospital of South Manchester, Manchester, UK
3Hospital
Port Dickson, Negeri Sembilan, Malaysia
*Corresponding
author: Cal Robinson, University of Manchester, Manchester, UK; Tel: 44 0 161 275 8258; E-mail: [email protected]
Rec date: Dec 23, 2014, Acc date: Dec 24, 2014, Pub date: Dec 26, 2014
Copyright: © 2014 Robinson C, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted
use, distribution, and reproduction in any medium, provided the original author and source are credited.
Introduction
Greater understanding of the pathophysiology underlying
musculoskeletal conditions provides the opportunity for more
targeted, advanced treatment options. When lateral epicondylitis was
first described by Runge in 1873 it was thought to represent
inflammation of the common extensor origin of the forearm [1]. This
has been subsequently disproved histopathologically, and the term
epicondylitis is now itself a misnomer [2-4]. It is instead a form of
tendinosis, resulting from repetitive stress-mediated degeneration of
the common extensor tendon origin [5,6]. The formation of microtears triggers a complex collagen-mediated histopathological reaction;
known as angiofibroblastic hyperplasia [2-5].
Traditionally, lateral epicondylitis has been treated conservatively
with good outcomes in 80% of patients [7,8]. Conservative treatment
involves rest (avoidance of aggravating activities and behaviour
modification), physiotherapy, bracing, analgesia and non-steroidal
anti-inflammatory medications [9,10]. For patients refractory to
conservative treatment, injections with corticosteroids are still
routinely used. Ultimately, patients not responding to non-operative
measures may require surgical intervention [5,9]. A variety of
procedures (open or arthroscopic) have been described, with no clear
consensus established on a gold-standard operation [5].
Greater pathophysiological understanding has promoted the use of
a number of alternative modalities focused on augmenting soft tissue
healing. These include extracorporeal shock wave therapy, laser
therapy, botulinum toxin injection, topical nitrates, autologous blood
injection and finally, Platelet-rich Plasma (PRP) injection [5,11]. These
therapies have a theoretical advantage over corticosteroids, due to the
lack of evidence for inflammation in lateral epicondylitis. Given that
the evidence base for individual surgical procedures remains weak,
alternative injections may also prove beneficial in reducing the
number of refractory cases requiring surgery.
PRP is derived from the centrifugication of autologous blood,
resulting in higher platelet concentrations than that of the original
sample [11]. The rationale behind its use lies in its potential ability to
provide growth factors to the relatively avascular diseased tendon, thus
promoting tissue healing and tendon regeneration [11]. PRP has
gained a significant amount of attention in orthopaedic and sports
medicine communities in the past decade, largely due to the promising
results of pre-clinical laboratory studies [5,11,12]. In practice, PRP is
applied by single or multiple injections to the area of maximal
tenderness [5].
While PRP therapy for tendinopathies has attracted significant
scientific exposure in recent years, fundamental inconsistencies still
Orthop Muscul Syst
ISSN:2161-0533 OMCR, an open access journal
exist within the literature. Authors continue to question the efficacy of
PRP for refractory tendinopathies, while leaving a number of key
questions unaddressed. By shifting our focus to answering these
questions, we may improve our understanding of the clinical role of
PRP therapy. We will attempt to highlight a number of the issues
within the current literature; including variable preparation methods
and PRP solutions, inconsistent control group interventions, the use of
adjunctive physiotherapy, and its comparison against autologous
blood injections.
PRP preparations
One key shortcoming found across studies analysing the efficacy of
PRP is significant variability between preparation methods and final
platelet concentration. Significant differences have been demonstrated
between the White Blood Cell (WBC) and growth factor levels
produced using various commercial PRP separation systems [13,14].
Studies have differed in the quantities of PRP injected (ranging from
1.5 mL to 3.5 mL), either alone or in combination with variable
amounts of local anaesthetic and/or epinephrine [15-19]. The number
of injections given and time intervals between injections also varies
between studies.
At present, PRP preparations differ on the basis of their platelet
concentration [20-23]. Further, the relative concentrations of different
growth factors, the method of platelet activation (exogenous vs.
endogenous), the degree of WBC contamination and PRP storage
conditions are all implicated to affect the healing potential of PRP
injection, and none are standardised across studies [20,21,23].
Additionally, the inter-person variability in growth factor
concentration has been demonstrated to be as high as 50% between
samples obtained from individuals in the same study [21].
While one might assume that increasing the platelet concentration
of the PRP injection would promote greater tissue healing and better
outcomes, this has not been demonstrated in research and the optimal
platelet concentration has not been established. Yamaguchi et al.
(2010) conducted an animal study focused on the effect of different
platelet concentrations on intestinal anastamotic healing [24]. Perhaps
counter-intuitively, they found that their low platelet concentration
group exhibited the highest levels of wound healing, whereas higher
concentrations were found to inhibit wound healing in relation to
their control. This suggests that lower platelet concentrations than
initially thought may provide the best therapeutic results. Research on
optimizing platelet concentrations in PRP, however, is currently
lacking and variation between clinical trials may skew results and
mask the genuine efficacy of an optimized PRP injection.
Volume 3 • Issue 4 • 1000e113
Citation:
Robinson C, Mathavan G, Pillai A (2014) Platelet-Rich Plasma Therapies in Lateral Epicondylitis: Are we Asking the Right Questions?.
Orthop Muscul Syst 3: e113. doi:10.4172/2161-0533.1000e113
Page 2 of 3
Controversy also exists over the potential benefit or harm of WBC
contamination of PRP preparations. Some authors argue that higher
WBC concentrations may provide antimicrobial action and increase
the concentrations of growth factors present [21]. Others have argued
that WBC contamination will augment inflammation and pain and
further impede tissue healing [19]. No consensus has been established
within the literature on the subject.
A recent Cochrane review [11] reported that “currently there is no
consensus regarding standardisation for research or clinical use. There
are several preparation methods for platelet products, which are likely
to be a source of heterogeneity for the assessment and comparison of
the effectiveness of PRT”. It goes on to recommend that
standardisation of PRP preparation methods is required for the
reliable assessment of its efficacy.
Control groups
The lack of congruency between authors on suitable control groups
additionally limits possible comparison and clinical application of
their findings. Many studies have used either corticosteroid or local
anaesthetic (typically bupivicaine) injections as their control arm
[16,18,25,26]. However, both have come under recent criticism and are
suggested to generate worse long-term clinical outcomes than
conservative treatment alone. Lehner et al. (2013) reported on the
detrimental effects of bupivicaine on tendon tissue in animal studies,
demonstrating that bupivicaine injection increased the tendon
vulnerability to injury and overload stress [27]. The use of
corticosteroid injections to treat various tendinopathies, while still
commonplace in clinical practice, has been repeatedly challenged by
authors [28]. It is logical to predict that an anti-inflammatory
substance should confer no benefit in the treatment of a noninflammatory, degenerative condition. Coombes et al. (2010)
substantiated these attitudes by performing a systematic review on the
efficacy and risk associated with the use of corticosteroid injections in
the treatment of tendinopathies [29]. They concluded that while
corticosteroids improve symptoms in the short-term following
injection, they resulted in worse intermediate and long-term clinical
outcomes than no intervention. As these control groups cannot be
validated, the true effect of PRP injections may be exaggerated within
these studies.
Adjunctive physiotherapy
No agreement has been reached on the efficacy of adjunctive
physiotherapy or exercise following PRP injection [30]. Given the
mechanism of PRP therapy it would seem logical to prescribe a period
of relative rest to allow sufficient healing of the affected tendon,
followed by a stretching and strengthening programme to improve
functional outcomes. The precise amounts of time allocated to each
phase, as well as any benefit provided by initial rest have not been
analysed. Further, significant variability and incomplete reporting
exists between studies [15,18,25,26]. This further shrouds the efficacy
of an optimized PRP therapy in lateral epicondylitis.
PRP vs. autologous blood injections
Of all of the alternative therapies proposed for the treatment of
refractory tendinopathies, PRP has received the greatest amount of
attention in orthopaedic and sports medicine communities. Based on
promising pre-clinical data, it has become a highly attractive potential
treatment modality. As such, research in alternative injection therapies
Orthop Muscul Syst
ISSN:2161-0533 OMCR, an open access journal
has focused on comparing either PRP against control interventions or
PRP against autologous blood injections. Research focused on the
efficacy of autologous blood against control interventions is sparse and
of lower quality. However, PRP has not been definitively proven to be
more efficacious in the treatment of lateral epicondylitis than
autologous blood [15,19,31,32]. Three systematic reviews comparing
the modalities have concluded that the evidence available is
insufficient to justify the use of PRP over autologous blood [17,30,33].
In theory, this may relate to the healing benefit conferred by lower
platelet concentrations than initially thought.
This is of great significance when considering the cost efficacy of
the individual modalities. It is estimated that PRP therapy for an
individual patient costs an average of $1000 (USD) [16]. In contrast,
autologous blood injection requires little more than a syringe and five
minutes of a physician’s time. Given that it has been shown to hold
equivalent clinical outcomes to PRP and provide significant
symptomatic improvement over no intervention [32,34], autologous
blood injection represents a much more cost effective treatment
option. Until PRP can be definitively proven to be more efficacious, it
would seem sensible to focus research on establishing the clinical role
of autologous blood in lateral epicondylitis.
PRP for other conditions
Although lateral epicondylitis has been the focus of this editorial,
PRP therapies have become widely used for a variety of acute and
chronic musculoskeletal injuries [11,12,22]. Lengthy recovery times
and residual symptoms, combined with patient demand for an
expedited return to activities has increased the popularity of PRP
dramatically in the past decade. PRP therapies used can be broadly
segregated into a primary intervention for tendinopathies (eg. medial/
lateral epicondylitis, Achilles and patellar tendinopathy) or an
augmentation procedure for surgical intervention (eg. rotator cuff
repair, subacromial decompression, ACL reconstruction and repair of
Achilles tendon rupture) [11]. Overall, no significant functional
improvement has been consistently demonstrated in favour of PRP
therapies used for either purpose [11]. Short-to-medium term pain
reduction in favour of PRP has been demonstrated by a number of
authors, although is challenged by others [11]. PRP has not been
shown to increase the risk of adverse events over controls [11]. The
recent Cochrane review reported that “the available evidence is
insufficient to indicate whether the effects of PRT will differ
importantly in individual clinical conditions [11]. All areas of PRP
research are plagued by the same shortcomings as for lateral
epicondylitis research. Standardisation of preparation methods and
follow-up protocol across studies is required to significantly advance
our understanding of PRP’s clinical role for a variety of
musculoskeletal conditions.
Conclusions
A number of unanswered questions continue to exist relating to the
use of PRP therapy for refractory tendinopathies. The lack of
consensus over PRP preparation methods and equipment, the frequent
use of inappropriate control interventions, and the poorly established
role of adjunctive physiotherapy limits the amount of comparison
possible between studies and weakens the evidence supporting the
clinical use of PRP for lateral epicondylitis. Additionally, the focus of
research on PRP therapy has distracted attention away from
autologous blood injection studies. Despite being reported to hold
equivalent clinical outcomes and being significantly more cost
Volume 3 • Issue 4 • 1000e113
Citation:
Robinson C, Mathavan G, Pillai A (2014) Platelet-Rich Plasma Therapies in Lateral Epicondylitis: Are we Asking the Right Questions?.
Orthop Muscul Syst 3: e113. doi:10.4172/2161-0533.1000e113
Page 3 of 3
effective, its clinical role remains obscure. We further recommend that
future research focus on establishing the optimal concentrations of
platelets, growth factors and WBCs in PRP preparations. Clinical trials
should avoid the use of corticosteroid or bupivicaine as control
interventions and should attempt to define the optimal programme of
adjunctive physiotherapy.
18.
19.
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